Exploring the role of Janus kinase (JAK) in atopic dermatitis: a review of molecular mechanisms and therapeutic strategies

References

• Eichenfield LF, DiBonaventura M, Xenakis J, et al. Costs and treatment patterns among patients with atopic dermatitis using advanced therapies in the United States: analysis of a retrospective claims database. Dermatol Ther . 2020; 10(4):791–806.
   PubMed Web of Science ®Google Scholar
• Akinlade B, Guttman‐Yassky E, Bruin‐Weller M, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019; 181(3):459–473.
   PubMed Web of Science ®Google Scholar
• Šteňová E, Tarabčáková L, Babál P, et al. Hypereosinophilic syndrome—a rare adverse event of anti-cytokine treatment in rheumatoid arthritis resolved after Janus kinase inhibitor therapy. Clin Rheumatol. 2020; 39(11):3507–3510.
   PubMed Web of Science ®Google Scholar
• Freidin M, Kessler JA. Cytokine regulation of substance P expression in sympathetic neurons. Proc Natl Acad Sci U S A. 1991; 88(8):3200–3203.
   PubMed Web of Science ®Google Scholar
• Silvennoinen O, Haikarainen T, Virtanen A. Aiming for the pocket. Nat Chem Biol. 2022;18(12):1296–1297.
   PubMed Web of Science ®Google Scholar
• Darnell JE. STATs and gene regulation. Science. 1997; 277(5332):1630–1635.
   PubMed Web of Science ®Google Scholar
• Koride S, Nayak S, Banfield C, et al. Evaluating the role of Janus kinase pathways in platelet homeostasis using a systems modeling approach. CPT Pharmacometrics Syst Pharmacol. 2019;8(7):478–488.
   PubMedGoogle Scholar
• Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017; 16(12):843–862.
   PubMed Web of Science ®Google Scholar
• Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021; 66(1):402.
   PubMed Web of Science ®Google Scholar
• Chen M, Dai SM. A novel treatment for psoriatic arthritis: Janus kinase inhibitors. Chin Med J. 2020; 133(8):959–967.
   PubMed Web of Science ®Google Scholar
• Garcia-Melendo C, Cubiró X, Puig L. Janus kinase inhibitors in dermatology: part 1—general considerations and applications in vitiligo and alopecia areata. Actas Dermo-Sifiliográficas (English Edition). 2021; 112(6):503–515.
   Google Scholar
• Philips RL, Wang Y, Cheon H, et al. The JAK-STAT pathway at 30: much learned, much more to do. Cell. 2022; Oct185(21):3857–3876.
   PubMed Web of Science ®Google Scholar
• Tzeng HT, Chyuan IT, Lai JH. Targeting the JAK-STAT pathway in autoimmune diseases and cancers: a focus on molecular mechanisms and therapeutic potential. Biochem Pharmacol. 2021; Nov193:114760.
   PubMed Web of Science ®Google Scholar
• Cutolo M, Meroni M. Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis. JIR. 2013; 6:129–137. DOI:10.2147/JIR.S35901
   Google Scholar
• Shawky AM, Almalki FA, Abdalla AN, et al. A comprehensive overview of globally approved JAK inhibitors. Pharmaceutics. 2022; 14(5):1001.
   PubMed Web of Science ®Google Scholar
• Parganas E, Wang D, Stravopodis D, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998 ;93(3):385–395.
   PubMed Web of Science ®Google Scholar
• Guglielmelli P, Barosi G, Specchia G, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood. 2009; Aug114(8):1477–1483.
   PubMed Web of Science ®Google Scholar
• Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a Trinity. J Dermatol Sci. 2013; 70(1):3–11.
   PubMed Web of Science ®Google Scholar
• Otsuka A, Nomura T, Rerknimitr P, et al. The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis. Immunol Rev. 2017; 278(1):246–262.
   PubMed Web of Science ®Google Scholar
• Weidinger S, Beck LA, Bieber T, et al. Atopic dermatitis. Nat Rev Dis Primers. 2018; 4(1):1.
   PubMed Web of Science ®Google Scholar
• Sousa-Santos ACAF, Moreno AS, Santos ABR, et al. Parasite infections, allergy and asthma: a role for tropomyosin in promoting type 2 immune responses. Int Arch Allergy Immunol. 2020;181(3):221–227.
   PubMed Web of Science ®Google Scholar
• Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020; 50(1):5–14.
   PubMed Web of Science ®Google Scholar
• Furue M. Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4–JAK–STAT6/STAT3 axis: pathogenic and therapeutic implications in atopic dermatitis. JCM. 2020; Nov 209(11):3741.
   Google Scholar
• Chieosilapatham P, Kiatsurayanon C, Umehara Y, et al. Keratinocytes: innate immune cells in atopic dermatitis. Clin Exp Immunol. 2021 May 13;204(3):296–309.
   PubMed Web of Science ®Google Scholar
• Genois A, Haig M, Roches AD, et al. Case report of atopic dermatitis with refractory pruritus markedly improved with the novel use of clonidine and trimeprazine: dramatic relief of pruritus with clonidine. Pediatr Dermatol. 2014;31(1):76–79.
   PubMed Web of Science ®Google Scholar
• Nakashima C, Ishida Y, Kaku Y, et al. Dupilumab improved atypical fibrotic skin plaques in atopic dermatitis. Br J Dermatol. 2020;182(2):487–488.
   PubMed Web of Science ®Google Scholar
• Furue K, Ito T, Tsuji G, et al. The IL-13–OVOL1–FLG axis in atopic dermatitis. Immunology. 2019;158(4):281–286.
   PubMed Web of Science ®Google Scholar
• Bieber T. Interleukin‐13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020; 75(1):54–62.
   PubMed Web of Science ®Google Scholar
• Erickson S, Heul AV, Kim BS. New and emerging treatments for inflammatory itch. Ann Allergy Asthma Immunol. 2021; Jan126(1):13–20.
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Fölster-Holst R, Saint Aroman M, et al. Effects of a protein-free oat plantlet extract on microinflammation and skin barrier function in atopic dermatitis patients. J Eur Acad Dermatol Venereol. 2018; Apr32:1–15.
   PubMed Web of Science ®Google Scholar
• Nomura T, Honda T, Kabashima K. Multipolarity of cytokine axes in the pathogenesis of atopic dermatitis in terms of age, race, species, disease stage and biomarkers. Int Immunol. 2018; Aug 3030(9):419–428.
   PubMed Web of Science ®Google Scholar
• Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012; 130(6):1344–1354.
   PubMed Web of Science ®Google Scholar
• Halling AS, Loft N, Silverberg JI, et al. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol. 2021; 84(1):139–147.
   PubMed Web of Science ®Google Scholar
• Radi G, Simonetti O, Rizzetto G, et al. Baricitinib: the first jak inhibitor approved in Europe for the treatment of moderate to severe atopic dermatitis in adult patients. Healthcare. 2021; 9(11):1575.
   Web of Science ®Google Scholar
• Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-evere atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157(9):1047–1055.
   PubMed Web of Science ®Google Scholar
• Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101–1112.
   PubMed Web of Science ®Google Scholar
• Mohney LA, Singh R, Feldman SR. Review of ruxolitinib in the treatment of atopic dermatitis. Ann Pharmacother. 2023; 57(2):207–216.
   PubMed Web of Science ®Google Scholar
• Tsoi LC, Rodriguez E, Degenhardt F, et al. Atopic dermatitis is an IL-13–dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol. 2019; 139(7):1480–1489.
   PubMed Web of Science ®Google Scholar
• Di Salvo E, Ventura-Spagnolo E, Casciaro M, et al. IL-33/IL-31 axis: a potential inflammatory pathway. Mediators Inflamm. 2018;2018:1–8.
   Web of Science ®Google Scholar
• Owji S, Caldas SA, Ungar B. Management of atopic dermatitis: clinical utility of ruxolitinib. J Asthma Allergy. 2022;15:1527–1537.
   PubMed Web of Science ®Google Scholar
• Kirito K. Recent progress of JAK inhibitors for hematological disorders. Immunol Med. 2022:1–12. DOI:10.1080/25785826.2022.2139317
   PubMedGoogle Scholar
• Tanimoto A, Shinozaki Y, Nozawa K, et al. Improvement of spontaneous locomotor activity with JAK inhibition by JTE-052 in rat adjuvant-induced arthritis. BMC Musculoskelet Disord. 2015;16(1):339.
   PubMedGoogle Scholar
• Nakagawa H, Nemoto O, Igarashi A, et al. Long‐term safety and efficacy of delgocitinib ointment, a topical janus kinase inhibitor, in adult patients with atopic dermatitis. J Dermatol. 2020;47(2):114–120.
   PubMed Web of Science ®Google Scholar
• Eichner A, Wohlrab J. Pharmacology of inhibitors of janus kinases – part 1: pharmacokinetics. J Dtsch Dermatol Ges. 2022; Nov20(11):1485–1499.
   Web of Science ®Google Scholar
• Mohamed MEF, Klünder B, Othman AA. Clinical pharmacokinetics of upadacitinib: review of data relevant to the rheumatoid arthritis indication. Clin Pharmacokinet. 2020 May;59(5):531–544.
   PubMed Web of Science ®Google Scholar
• Shi JG, Chen X, Emm T, et al. The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in healthy volunteers. J Clin Pharmacol. 2012; 52(6):809–818.
   PubMed Web of Science ®Google Scholar
• Chimalakonda A, Burke J, Cheng L, et al. Selectivity profile of the tyrosine kinase 2 inhibitor deucravacitinib compared with janus kinase 1/2/3 inhibitors. Dermatol Ther. 2021;11(5):1763–1776.
   PubMed Web of Science ®Google Scholar
• Eichner A, Wohlrab J. Pharmacology of inhibitors of janus kinases – part 2: pharmacodynamics. J Dtsch Dermatol Ges. 2022; 20(12):1621–1631.
   Google Scholar
• Winthrop KL, Nash P, Yamaoka K, et al. Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials. Ann Rheum Dis. 2022; 81(2):206–213.
   PubMed Web of Science ®Google Scholar
• Alves C, Penedones A, Mendes D, et al. The safety of systemic janus kinase inhibitors in atopic dermatitis: a systematic review and network meta-analysis. Eur J Clin Pharmacol. 2022; 78(12):1923–1933.
   PubMed Web of Science ®Google Scholar
• Toyama N, Shiraki K. and Epidemiology of herpes zoster and its relationship to varicella in Japan: a 10-year survey of 48,388 herpes zoster cases in Miyazaki prefecture. J Med Virol. 2009; 81(12):2053–2058.
   PubMed Web of Science ®Google Scholar
• Thompson RR, Kong CL, Porco TC, et al. Herpes zoster and postherpetic neuralgia: changing incidence rates from 1994 to 2018 in the United States. Clin Infect Dis. 2021;73(9):e3210–7–e3217.
   Web of Science ®Google Scholar
• Bing N, Zhou H, Chen X, et al. Contribution of a european‐prevalent variant near CD83 and an east asian–prevalent variant near IL17RB to herpes zoster risk in tofacitinib treatment: results of genome‐wide association study meta‐analyses. Arthritis Rheumatol. 2021; Jul73(7):1155–1166.
   PubMed Web of Science ®Google Scholar
• Chang P, Huang S, Chang P, et al. Safety considerations of systemic Janus kinase inhibitors in atopic dermatitis applications. J Dermatol. 2021; 48(11):1631–1639.
   PubMed Web of Science ®Google Scholar
• Lee SD, Ahn HJ, Shin MK. A case series of acne following Janus kinase inhibitors in patients with atopic dermatitis. JAAD Case Rep. 2022; 30:11–16.
   PubMedGoogle Scholar
• Thyssen JP, Yosipovitch G, Paul C, et al. Patient‐reported outcomes from the JADE COMPARE randomized phase 3 study of abrocitinib in adults with moderate‐to‐severe atopic dermatitis. J Eur Acad Dermatol Venereol. 2022;36(3):434–443.
   PubMed Web of Science ®Google Scholar
• Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022; 386(4):316–326.
   PubMed Web of Science ®Google Scholar
• Alharthi S, Turkmani M, AlJasser MI. Acne exacerbation after tofacitinib treatment for alopecia areata. Dermatol Reports. 2022; [cited 14(2):9396. Available fromhttps://www.pagepress.org/journals/index.php/dr/article/view/9396
   PubMedGoogle Scholar
• Snast I, Dalal A, Twig G, et al. Acne and obesity: a nationwide study of 600,404 adolescents. J Am Acad Dermatol. 2019;81(3):723–729.
   PubMed Web of Science ®Google Scholar
• Saleiro D, Platanias LC. Intersection of mTOR and STAT signaling in immunity. Trends Immunol. 2015; 36(1):21–29.
   PubMed Web of Science ®Google Scholar
• Choa R, Tohyama J, Wada S, et al. Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion. Science. 2021; 373(6554):eabd2893.
   PubMed Web of Science ®Google Scholar